SURPASS-4: Tirzepatide Reduces A1C, Body Weight in Type 2 Diabetes

By Dave Quaile, /alert Contributor
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Treatment with tirzepatide reduced hemoglobin A1C and body weight from baseline compared with titrated insulin glargine among patients with type 2 diabetes with increased cardiovascular risk, according to new data.

Tirzepatide is a novel investigational once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist that integrates the actions of the GIP and GLP-1 incretins into a single molecule, representing a new class of medicines being studied for the treatment of type 2 diabetes.

"Tirzepatide delivered impressive results in this study, providing superior A1C reductions compared to insulin glargine – as well as the addition of significant weight loss – in people with type 2 diabetes who have increased cardiovascular risk," John Doupis, MD, PhD, director of the diabetes division and clinical research center at the Iatriko Paleou Falirou Medical Center in Athens, Greece, said in a press release. "Type 2 diabetes is a complex condition that requires personalized approaches to treatment, and results from SURPASS-4 demonstrate the potential of tirzepatide to be an important option to help reduce A1C and weight for people with type 2 diabetes on one or up to three oral medicines.”

The SURPASS-4 trial compared the safety and efficacy of three tirzepatide doses to titrated insulin glargine in over 2,000 participants with type 2 diabetes who had increased CV risk and were treated with between one and three oral antihyperglycemic medications, according to the release. 

The mean duration of diabetes among participants was 11.8 years. Patients had a median baseline A1C of 8.52% and a median baseline weight of 90.3 kg. Over 85% of participants had a history of CV events. 

The researchers titrated insulin dose among patients in the insulin glargine cohort following a treat-to-target algorithm with the goal of fasting blood glucose below 100 mg/d. 

Patients were given 10 units of insulin glargine per day at baseline and the mean dose of insulin glargine at 52 weeks was 43 units per day.

The SURPASS-4 trial achieved all primary and key secondary endpoints. When compared to insulin glargine, all three doses of tirzepatide led to superior A1C and body weight reductions compared to both estimandsii. 

At the highest dose of tirzepatide, A total of 91% of participants achieved an A1C less than 7 percent when receiving the highest dose of tirzepatide and 43% achieved an A1C less than 5.7 percent. 

According to the study, hypoglycemia less than 54 mg/dL at 52 weeks was reported in 6.7% (5 mg), 5.5% (10 mg) and 6.5% (15 mg) of participants in the tirzepatide arms, respectively and in 15% of participants in the insulin glargine arm. Patients who had background therapy of a sulfonylurea reportedly more commonly experienced episodes of hypoglycemia.

At 52 weeks, the most commonly reported adverse events among patients in the tirzepatide cohort were gastrointestinal-related and were considered mild to moderate in severity by researchers.

“These strong results reinforce our belief that tirzepatide has the potential to be an exciting treatment for people living with type 2 diabetes,” Mike Mason, president, Lilly Diabetes, said in a press release. “We look forward to meeting our goal of bringing an important new therapy to people living with this condition, including sharing more detailed results at scientific congresses and submitting to regulatory authorities later this year.”

Disclosure: Mason is president of Lilly Diabetes. 


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